The use of glucose by the brain serves as an energy source and is requisite for the formation of several neurotransmitters. Aging may be associated with detrimental alterations in hepatic glucose production, cerebral glucose uptake, and related abnormalities on neuronal transmission. In contrast, endurance training is associated with enhanced hepatic gluconeogenic capacity. The proposed studies will examine the effects of endurance training and aging on the gluconeogenic response to distinct hormones and hormone concentrations in isolated hepatocytes. The extent of pyruvate kinase-L inhibition and alterations in the activity of phosphodiesterase and adenyl cyclase activation will be examined to elucidate the ability of training to attenuate the age related decline in hepatic gluconeogenesis. The overall aim is to delineate the training induced adaptations which enable the liver to enhance the response to hormone stimulation. Investigation of the specific enzyme regulatory site (pyruvate kinase-L) and molecular mechanisms involved in enzyme inhibition will lead to further understanding of mechanisms responsible for the enhanced gluconeogenic capacity of the liver following training.